Latent Mycobacterium tuberculosis infection presents one of the largest challenges for tuberculosis control and novel antimycobacterial drug development. A series of pyrano[3,2-b]indolone-based compounds was designed and synthesized via an original eight-step scheme. The synthesized compounds were evaluated for their in vitro activity against M. tuberculosis strains H37Rv and streptomycin-starved 18b (SS18b), representing models for replicating and nonreplicating mycobacteria, respectively. Compound 10a exhibited good activity with MIC99 values of 0.3 and 0.4 μg/mL against H37Rv and SS18b, respectively, as well as low toxicity, acceptable intracellular activity, and satisfactory metabolic stability and was selected as the lead compound for further studies. An analysis of 10a-resistant M. bovis mutants disclosed a cross-resistance with pretomanid and altered relative amounts of different forms of cofactor F420 in these strains. Complementation experiments showed that F420-dependent glucose-6-phosphate dehydrogenase and the synthesis of mature F420 were important for 10a activity. Overall these studies revealed 10a to be a prodrug that is activated by an unknown F420-dependent enzyme in mycobacteria.
- Klíčová slova
- antimycobacterial activity, latent tuberculosis, pyrano[3,2-b]indolone,
- MeSH
- antituberkulotika farmakologie MeSH
- latentní tuberkulóza * MeSH
- lidé MeSH
- Mycobacterium tuberculosis * genetika MeSH
- tuberkulóza * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antituberkulotika MeSH
A new arrangement of the INCAT (inside needle capillary adsorption trap) device with Carbopack X and Carboxen 1000 as sorbent materials was applied for sampling, preconcentration and injection of C6C19n-alkanes and their monomethyl analogs in exhaled breath samples. For the analysis both GC-MS/MS and GC×GC-FID techniques were used. Identification of the analytes was based on standards, measured retention indices and selective SRM transitions of the individual isomers. The GC-MS/MS detection limits were in the range from 2.1 pg for n-tetradecane to 86 pg for 5-methyloctadecane. The GC×GC-FID detection limits ranged from 19 pg for n-dodecane to 110 pg for 3-methyloctane.
- Klíčová slova
- Exhaled breath, INCAT, Monomethylalkanes, Needle trap, n-Alkanes,
- MeSH
- alkany analýza chemie MeSH
- dechové testy metody MeSH
- lidé MeSH
- limita detekce MeSH
- plynová chromatografie s hmotnostně spektrometrickou detekcí metody MeSH
- reprodukovatelnost výsledků MeSH
- tandemová hmotnostní spektrometrie metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- alkany MeSH
A simple two-step method for the derivatization of polar compounds (lactate, alanine, glycerol, succinate and glucose) using hexamethyldisilazane (HMDS) and N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) was developed. This method allows direct derivatization of aqueous samples wihout sample pretreatment. The method was used for the analysis of the metabolites of the unicellular organism Trypanosoma brucei. The limits of detection by GC-MS/MS analysis were in the range of 0.02 mg L(-1) for glucose to 0.85 mg L(-1) for lactate.
- Klíčová slova
- Aqueous samples, GC–MS/MS analysis, Metabolites, Protozoa, Trimethylsilylation,
- MeSH
- alanin analýza chemie metabolismus MeSH
- glukosa analýza chemie metabolismus MeSH
- kyselina mléčná analýza chemie metabolismus MeSH
- limita detekce MeSH
- organické sloučeniny křemíku chemie MeSH
- plynová chromatografie s hmotnostně spektrometrickou detekcí metody MeSH
- reprodukovatelnost výsledků MeSH
- trimethylsilylové sloučeniny chemie MeSH
- Trypanosoma brucei brucei chemie metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- alanin MeSH
- glukosa MeSH
- hexamethylsilazane MeSH Prohlížeč
- kyselina mléčná MeSH
- N,N-bis(trimethylsilyl)-2,2,2-trifluoroacetamide MeSH Prohlížeč
- organické sloučeniny křemíku MeSH
- trimethylsilylové sloučeniny MeSH
